Mosquito-borne diseases continue to cause significant morbidity and mortality worldwide despite on-going control efforts. In 2015, there were >200 million cases of malaria worldwide, causing nearly half a million deaths, with most of the deaths occurring among children under the age of 5 years. Mosquitoes also transmit arboviruses, including dengue, yellow fever, West Nile virus, chikungunya, Rift Valley fever, Japanese encephalitis, and Zika virus. The recent outbreak of Zika virus in Central and South America, as well as the Caribbean, serves as a reminder of how quickly these viruses can spread and how difficult they can be to control. This past year we initiated a Phase I study of a novel universal mosquito-borne disease vaccine. Through modulation of the immune system after a mosquito feeding, this vaccine targets the vector saliva and may provide prophylaxis against multiple arboviral and protozoal diseases. In addition the vaccine potentially leads to a reduced mosquito lifespan after feeding therefore also reducing transmission of these diseases. This protocol marks the first time a vaccine targeting mosquito saliva has been tested in humans and the first time clean mosquito feedings on humans have been performed in the NIH Clinical Center. In addition to this protocol we have initiated a close collaboration with LMVR and have been awarded an NIH Bench To Bedside award to perform a follow up clinical study in the NIH Clinical Center to evaluate the effect on the immune response of multiple exposures to the same vector. This study will include the evaluation of two species of mosquito as well as sandflies, the vector of leishmania. This study will be instrumental in further understanding how vaccination strategies that target vector saliva may work in individuals from endemic disease areas.